4,9-ETHANO-BENZO(F)ISOINDOLE DERIVATIVES AS FARNESYL TRANSFERASE INHIBITORS

摘要

PCT No. PCT/FR96/01062 Sec. 371 Date Jul. 23, 1998 Sec. 102(e) Date Jul. 23, 1998 PCT Filed Jul. 8, 1996 PCT Pub. No. WO97/03050 PCT Pub. Date Jan. 30, 1997Novel products of formula (I): preparation thereof and pharmaceutical compositions containing said products are disclosed. In formula (I), R is a group of formula -(CH2)m-X1-(CH2)n-Z, where X1 is a simple bond or O or S, n is 0 or 1 and n is 0, 1 or 2, the CH2 groups being optionally substituted by carboxy, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, amino, alkylamino or dialkylamino, and Z is carboxy, COOR4, where R4 is alkyl, or CON(R5)(R6), where R5 hydrogen or alkyl and R6 is hydrogen or optionally substituted alkyl, or else R5 is hydrogen or alkyl and R6 is hydroxy, optionally substituted alkoxy or amino, or PO(OR7)2, where R7 is hydrogen or alkyl; or a group -NH-CO-T where T is hydrogen or optionally substituted alkyl; or else a group (a); R1 and R2 are hydrogen or halogen or optionally substituted alkyloxy or alkyl, or else R1 and R2 in the ortho positions form a heterocyclic ring containing 1 or 2 optionally substituted hereoatoms, or R1 is hydrogen or halogen or optionally substituted alkyloxy or alkyl, and R2 is thioalkyl; R3 is hydrogen or halogen or alkyl alkenyl, alkyloxy, alkylthio, carboxy or alkyloxycarbonyl; X is O or S or -NH-, -CO-,methylene, ethylene, alkylidene or 1,1-cycloalkyl; and Y is O or S. The novel products of formula (I) are farnesyl transferase inhibitors having remarkable antitumoral and antineoplastic properties.